EV71 has caused large epidemics with lots of fatal cases and cases with sequelae. However, the clinical syndromes and severity of the same EV71 strain are very diverse, ranging from asymptomatic (71%) to fatal (0.05%) disease, and the pathogenesis remains unknown. In addition, the severe or fatal case incidence varies significantly differently in different areas of Taiwan. Although some viral virulence studies were performed, no clear viral virulence factor has been found. Therefore, host factors may be important to the clinical outcomes of EV71 infections. In addition, there were significantly different incidences of severe or fatal cases in different areas of Taiwan, for example, significantly more fatal or severe cases occurred in the central or southern Taiwan in comparison with in northern Taiwan. Whether this is related to host factors, social, behavioral or environmental factors remains unanswered. To find the most important factors associated with EV71 susceptibility, a thorough study involving genetics, social, behavioral or environmental factors among different areas of Taiwan is warranted and the findings will provide future prevention of EV71 and give help on early precaution and treatment of EV71.